Abstract

HLA-B*57 control of HIV involves enhanced CD8+ T cell responses against infected cells, but extensive heterogeneity exists in level of HIV control among B*57+ individuals.

Using whole genome sequencing of untreated B*57+ HIV-1 infected controllers and non-controllers, we identified a single variant (rs643347A/G) encoding an isoleucine to valine substitution at position 47 (I47V) of the inhibitory killer cell immunoglobulin-like receptor, KIR3DL1, as the only significant modifier of B*57 protection.

The association replicated in an independent cohort and across multiple outcomes. The modifying effect of I47V was confined to B*57:01, and was not observed for the closely related B*57:03. Positions 2, 47, and 54 track one another nearly perfectly, and two KIR3DL1 allotypes differing only at these three positions showed significant differences in binding B*57:01 tetramers, where the protective allotype showed lower binding.

Thus, variation in an immune natural killer cell receptor that binds B*57:01 modifies its protection. These data speak to exquisite specificity of KIR-HLA interactions in human health and disease

By Linda Nordling, 2 December 2017, Quartz Africa. Antiretrovirals 'the drugs used to keep HIV in check' don't only prevent people from getting AIDS; they also keep virus levels low, making those taking them less likely to pass the infection to others. Press coverage of our KRISP paper Iwuji et al. (Lancet HIV 2017).

By Katharine Child, 05 December 2017. SA's policy to reduce HIV infections is to do what the UN recommends, which is to get 90% of people tested, 90% of HIV-positive people taking antiretrovirals and 90% of those on treatment taking it properly so they are not infectious. Press coverage of our KRISP paper Iwuji et al. (Lancet HIV 2017).